Summary of work: Longitudinal measurements of cognition, brain glucose metabolism as determined with positron emission tomography (PET), and brain anatomy using magnetic resonance imaging were conducted in ten Down's syndrome (DS) subjects initially older than 40 years of age. Changes in memory test scores over seven years preceded the appearance of overt dementia in two subjects, indicating that a pre-dementia prodrome can be identified in subjects with 100% risk of developing Alzheimer's disease (AD). Predementia changes were confirmed by submitting the non-demented subjects to audiovisual stimulation while measuring regional glucose metabolism with PET.